Depositing therapeutic drugs on the olfactory epithelium has been shown to lead to rapid and direct uptake into the brain. This direct nose-to-brain delivery route bypasses the blood-brain-barrier, which keeps a majority of drugs or drug candidates from reaching the brain in any significant concentrations. Many studies, including those of the present inventors, have shown that depositing a drug on the olfactory epithelium, while minimizing drug absorption on the respiratory epithelium, is key to maximizing the fraction of drug that bypasses the blood-brain-barrier and reaches the brain.
Currently there are no suitable nasal delivery devices that sufficiently target the olfactory region of the nasal cavity while avoiding the lungs and respiratory area of the nasal cavity. The olfactory region is a narrow space at the top of the nasal cavity taking up about 10% of the total surface area of the nasal cavity. In addition, when a subject breaths in through the nose, the inhaled air travels primarily along the lower part of the nasal cavity into the trachea and lung, thus, leaving the air in the olfactory region mainly undisturbed and stagnant in the olfactory region (and hence leading to a low fraction of olfactory drug exposure for drugs carried along the breath path).
The present disclosure overcomes the disadvantages associated with the anatomical impediments described above by providing pressurized olfactory drug delivery devices and methods for delivering pharmaceutical compounds to the olfactory epithelium.